VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1

被引：103

作者：

de Almodovar, Carmen Ruiz ^{[2
,3
]}

Fabre, Pierre J. ^{[1
,4
]}

Knevels, Ellen ^{[2
,3
]}

Coulon, Cathy ^{[2
,3
]}

Segura, Inmaculada ^{[2
,3
]}

Haddick, Patrick C. G. ^{[5
]}

Aerts, Liesbeth ^{[2
,3
]}

Delattin, Nicolas ^{[2
,3
]}

Strasser, Geraldine ^{[5
]}

Oh, Won-Jong ^{[6
]}

Lange, Christian ^{[2
,3
]}

Vinckier, Stefan ^{[2
,3
]}

Haigh, Jody ^{[7
,8
]}

Fouquet, Coralie ^{[9
]}

Gu, Chengua ^{[6
]}

Alitalo, Kari ^{[10
,11
]}

Castellani, Valerie ^{[12
]}

Tessier-Lavigne, Marc ^{[5
]}

Chedotal, Alain ^{[13
]}

Charron, Frederic ^{[1
,4
,14
,15
]}

Carmeliet, Peter ^{[2
,3
]}

机构：

[1] Univ Montreal, Inst Rech Clin Montreal IRCM, Montreal, PQ H2W 1R7, Canada

[2] Vesalius Res Ctr VRC, Lab Angiogenesis & Neurovascular link, KULeuven, Leuven, Belgium

[3] Vesalius Res Ctr VRC, Lab Angiogenesis & Neurovascular link, VIB, Leuven, Belgium

[4] Univ Montreal, Dept Med, Montreal, PQ H2W 1R7, Canada

[5] Genentech Inc, San Francisco, CA 94080 USA

[6] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[7] VIB, Dept Mol Biomed Res, Vascular Cell Biol Unit, Ghent, Belgium

[8] UGent, Dept Mol Biomed Res, Ghent, Belgium

[9] UPMC Paris 6, CNRS, UMR 7102, F-75005 Paris, France

[10] Biomedicum Helsinki, Mol Canc Biol Program, Helsinki, Finland

[11] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland

[12] Univ Lyon 1, CGMC, UMR, CNRS, F-69000 Lyon, France

[13] INSERM, Dept Dev, Inst Vis, UMR S968, F-75012 Paris, France

[14] McGill Univ, Div Expt Med, Dept Biol, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada

[15] McGill Univ, Program Neuroengn, Montreal, PQ H3A 2B2, Canada

来源：

NEURON | 2011年 / 70卷 / 05期

基金：

加拿大健康研究院;

关键词：

ENDOTHELIAL GROWTH-FACTOR; FOCAL ADHESION KINASE; SONIC HEDGEHOG; NEURAL-TUBE; EXPRESSION; SRC; ANGIOGENESIS; OUTGROWTH; NETRIN-1; GUIDANCE;

D O I：

10.1016/j.neuron.2011.04.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Growing axons are guided to their targets by attractive and repulsive cues. In the developing spinal cord, Netrin-1 and Shh guide commissural axons toward the midline. However, the combined inhibition of their activity in commissural axon turning assays does not completely abrogate turning toward floor plate tissue, suggesting that additional guidance cues are present. Here we show that the prototypic angiogenic factor VEGF is secreted by the floor plate and is a chemoattractant for commissural axons in vitro and in vivo. Inactivation of Vegf in the floor plate or of its receptor Flk1 in commissural neurons causes axon guidance defects, whereas Flk1 blockade inhibits turning of axons to VEGF in vitro. Similar to Shh and Netrin-1, VEGF-mediated commissural axon guidance requires the activity of Src family kinases. Our results identify VEGF and Flk1 as a novel ligand/receptor pair controlling connmissural axon guidance.

引用

页码：966 / 978

页数：13

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